Over the past year progress has been made in the following area: initially clearance experiments on dogs were carried out and clearly demonstrated that the natriuresis resulting from the simultaneous infusion of chlorothiazide and acetylcholine was much greater than that produced when these two agents were given separately. Indeed the effects of the two given together was considerably greater than that of the additive effects of the two agents given separately. This observation stimulated a careful examination of the effects of prior vasodilation on the potency of the thiazide diuretics- agents which are known to induce renal vasoconstriction in addition to decreased sodium reabsorption. Renal vasodilatation was induced by the infusion of acetylcholine into one renal artery. After determining the effects of the agent on renal sodium and water excretion along with changes in renal blood flow, chlorothiazide was added to the infusion. Intra- arterial infusion of acetylcholine alone or in combination with chlorothiazide depressed filtration fraction via an increase in renal blood flow with little change in glomerular filtration rate. Furthermore, the natriuresis which developed after the infusion of either acetylcholine alone or in combination with chlorothiazide could be blunted by the intrarenal infusion of hyperoncotic albumin. Recollection micropuncture experiments demonstrated that chlorothiazide when given alone produced a reduction in nephron GFR and absolute sodium reabsorption by the proximal tubule. However, the portional reduction in nephron GFR and absolute reabsorption resulted in no change in fractional reabsorption by the proximal tubule. When both acetylcholine and chlorothiazide were infused together, the chlorothiazide induced reduction in single nephron GFR was prevented. However, absolute reabsorption was strikingly depressed and so was fractional reabsorption. In the latter circumstance the depression of both absolute reabsorption and fractional reabsorption resulted in a greater delivery of sodium to more distal sites in the nephron. Additional micropuncture experiments were carried out which suggested that the reduction in superficial nephron absolute proximal reabsorption during acetychloline infusion could not be altered by simultaneous intrarenal arterial infusions of hyperoncotic albumin.